Prince Henry’s Prince Henry’s Institute of Medical Institute of Medical

ResearchResearch

Molecular genetic pathway of human sex determination Vince HarleyVince Harley

Embryonic gonad at 6 weeks & 7 weeks gestation

SRYtestis

ovary

SOX9

XY

XX

Swyer Syndrome ….Campomelic Dysplasia ….

What genes do SRY and SOX9 turn on and how?

Are SRY/SOX9 target genes intersex genes?

What is the molecular effect of clinical SRY/SOX9 mutations?

QUESTIONS:

Molecular biology, cell biology, protein biochemistry

human intersex patients, human EC lines, mouse knockouts,

TECHNIQUES& reagents

Female Reproductive Endocrinology Group: Prof. Jock Findlay, Dr Ann Drummond, Dr Paul Farnworth

Progesterone receptors

Androgen

PrimaryPrimordial

Secondary

Preovulatory

Corpus luteum

LH receptorsGranulosa cell

Atresia

Developing Follicles

Ovulation

Theca (androgens)

Oocyte

(progesteroneestrogen)

AndrogenOestrogenFSH receptors

The hormonal regulation of sperm production: David Robertson, Dr Peter Stanton, Dr Sarah Meachem, Prof Rob MacLaclan

Why are we interested?

• to understand the process of sperm production (spermatogenesis) in the healthy male

• to apply this knowledge to the development of treatments for male infertility

• to devise effective and reversible hormonal contraceptives for men

E2

Techniques• cell culture• transfection• RNA analysis• DNA / protein interaction

Breast cancer and estrogens: Prof Evan Simpson, Dr Colin Clyne

•Male reproductive system

•Dietary studies

•Adiposity

•Female reproductive system

The Aromatase knockout (ArKO) mouse

•Brain

Prof Evan Simpson, Dr Margaret Jones

Endocrine Cell Biology: Endocrine Cell Biology: Dr Chen ChenDr Chen Chen

• Type-II diabetesType-II diabetes – approx. 1 million Australians – approx. 1 million Australians – influence of adipocyte-derived factors on pancreatic influence of adipocyte-derived factors on pancreatic

ββ-cells-cells

– co-culture b-cells with fat cellsco-culture b-cells with fat cells

• GH deficiency in GH deficiency in ageing populationageing population – pituitary somatotropes in ArKO micepituitary somatotropes in ArKO mice

• OObesitybesity and GH deficiency and GH deficiency – leptin-from fat, orexin-from CNS, and ghrelin-from leptin-from fat, orexin-from CNS, and ghrelin-from

stomachstomach..

Uterine Biology GroupUterine Biology Group

Mission:Mission: to improve women’s healthto improve women’s health by- by-

• Increasing contraceptive choices for womenIncreasing contraceptive choices for women

• Improving fertility of infertile womenImproving fertility of infertile women

• Reducing / treating uterine bleeding Reducing / treating uterine bleeding problems problems

NP

d3.5

Imp

Inte

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Imp

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rd4.5 d5.5

Prof Lois Salamonsen, Dr Eva Dimitriadis, Dr Guiying Nie, Dr Naomi Morrison

1. Granulosa Cell Tumours (GCT)1. Granulosa Cell Tumours (GCT)

• 5% of malignant ovarian tumours

•Approach: tumour bank and cell lines

Our focus has been on:• profiles of gene expression: candidates & microarray • signalling pathways – constitutive activation• expression of ERβ

•coregulatory molecules• ERβ-induced genes

• mutation detection

Prof Peter Fuller

2. Mineralocorticoid Receptor Structure-2. Mineralocorticoid Receptor Structure-Function ProjectsFunction Projects

• ligand binding specificityligand binding specificity

• interdomain interactions• coregulatory proteins

Prof Peter Fuller

HypertensionHypertensionHypertrophyHypertrophy

Vascular InflammationVascular InflammationCardiac FibrosisCardiac Fibrosis

AldosteroneAldosterone

↑↑ ExtracellularExtracellularPotassiumPotassium

Fluid andFluid andelectrolyte electrolyte homeostasishomeostasis

3. Mineralocorticoids and heart disease3. Mineralocorticoids and heart disease

MRMR

RAASRAAS

In 2002, CVD claimed the lives of 50,000 Australians (~40% of all deaths)

Heart failure accounts for many of these deaths

Prof Peter Fuller and Dr Morag Young

PRINCE HENRY’S INSTITUTEPRINCE HENRY’S INSTITUTESTUDENT OPEN DAYSTUDENT OPEN DAY

Come and meet our researchers Come and meet our researchers and take a tour and take a tour of our facilitiesof our facilities

Tuesday 8 AUGUST 2006Tuesday 8 AUGUST 200610am – 12pm10am – 12pmFriday 11 AUGUST 2006Friday 11 AUGUST 20061pm – 3pm1pm – 3pm

Prince Henry’s InstitutePrince Henry’s InstituteLevel 4Level 443 – 51 Kanooka Grove43 – 51 Kanooka GroveClayton VIC 3168Clayton VIC 3168

www.princehenrys.org

Experimental approachExperimental approacheses

• Molecular biologyMolecular biology: RT-PCR: RT-PCR, RNAi (reduced , RNAi (reduced expression) and transfection (over-expression)expression) and transfection (over-expression);;

• HistochemistryHistochemistry: receptor and ligand localisation;: receptor and ligand localisation;

• Patch clampPatch clamp: ion channel and electrophysiology;: ion channel and electrophysiology;

• [Ca[Ca 2+2+]] ii: microphotometric recording for real-time and : microphotometric recording for real-time and confocal microscope for spatial distribution;confocal microscope for spatial distribution;

• ExocytosisExocytosis:: single cell-fluorescent Zinc (Insulin), single cell-fluorescent Zinc (Insulin), capacitance, amperometry; population-RIAcapacitance, amperometry; population-RIA..